Bisoprolol which is a highly selective β1-receptor antagonist in the sympathetic nerve has been used in amelioration of essential hypertension, angina pectoris, and arrhythmia, and its fumarate has been used as tablets for oral administration.
On the other hand, as a pharmaceutical preparation for treatment or prevention of diseases by administering a drug to the living body, a percutaneously absorbing preparation has attracted a great deal of attention in recent years, since drug metabolism by an initial effect passing through the liver and a variety of side effects can be avoided and the drug can be administered over a long period of time. Among them, a percutaneously absorbing adhesive preparation, in which an adhesive layer containing a drug is stuck on a skin surface, has been increasingly developed, since an operation of administration is easy and a dose can be strictly controlled. Such an adhesive preparation is required as it characteristic to have a releasability of a drug from an adhesive layer (transdermal permeability), stability of the drug contained in an adhesive layer with a lapse of day (prevention of decrease of the content of drug), stickiness on the skin surface (adhesiveness), appropriate cohesiveness for leaving no paste on the skin surface (prevention of leaving the paste after peeling-off), lower irritation to the skin (safety), and so on; thus, it is necessary to develop an adhesive pharmaceutical preparation which satisfies the above-required characteristics according to the kind of drugs.
As for a percutaneously absorbing pharmaceutical preparation, Patent Document 1 discloses an adhesive preparation containing menthol methylthiomethyl ether in order to enhance transdermal permeation of a physiologically active substance, for example, bisoprolol. Patent Document 2 has reported that addition of a third ingredient polyvinylpyrrolidone to a mixture of a particular rubber and polyacrylic acid in an adhesive preparation is capable of increasing the solubility of a drug without any adverse effect on the delivery rate of the drug, wherein the drug is exemplified by bisoprolol. In these patent documents, however, only bisoprolol has been exemplified as a drug, and no consideration has been made substantially on an adhesive preparation aimed to administer bisoprolol because an examination of the mutual interaction of bisoprolol with an adhesive itself has been done insufficiently. In addition, Patent Document 3 has proposed a percutaneously absorbing adhesive pharmaceutical preparation comprising bisoprolol in an acryl-type adhesive. In this preparation, however, it is difficult to say that stability of the drug and skin irritation caused by the drug have been investigated sufficiently, leaving room for improvement.
Patent Document 1: JP-A-11-29496
Patent Document 2: JP-T-09-511987
Patent Document 3: JP-A-2003-313122